Roche and Trimeris announce US sites and investigators for T-20 phase III study; activists want wider access to drug for sickest AIDS patients

17 April 2001. Related: Antiretrovirals, Treatment access.

By Ronald Baker, PhD and Brian Boyle, MD for HIV&Hepatitis.com

The entry inhibitors are a new class of anti-HIV drugs that block viral entry into the human cell. Several of these drugs are now in varying stages of testing, with T-20 in advanced clinical trials, others such as AMD 3100 and Schering C at relatively early stages of clinical trials, and still others that are in pre-clinical development.

Results of the first randomised trial of T-20, the entry inhibitor now entering Phase III testing, were presented at the 8th Annual Retrovirus Conference in Chicago, IL (February 4-8, 2001).

T-20, especially at higher doses appears to be additive to HAART in reducing viral load, with the 100 mg BID plus HAART arm achieving approximately a 0.6 log10 copies/mL greater decrease in viral load over the control arm (which just took HAART). There was no difference in the CD4 response. The findings of this study have to be tempered by the fact that statistical analysis was not performed to show a statistically significant difference “since the study was not powered to find a difference.” The primary adverse event associated with T-20 was a mild to moderate local skin reaction, and most patients did not discontinue therapy due to this problem.

T-20 Expanded Access Program

Hoffmann-LaRoche and Trimeris are co-developing T-20. The companies have announced an “expanded access” program for T-20 that will provide the drug to a limited number of patients who have multi-drug resistant HIV and low CD4 cell counts and who are unable to construct a successful treatment regimen with available HIV drugs. US and European activists have expressed bitter disappointment that the Roche/Trimeris plan will accommodate only a few hundred AIDS patients worldwide. FDA-approval and widespread (prescription) access to T-20 is not expected until late 2001 or early 2002.

The two companies cite complex drug manufacturing problems as the reason for the small size of the T-20 expanded access program. Traditionally these programs have provided pre-approval access to promising experimental AIDS drugs to several thousand of the most needy AIDS patients.

Although access to T-20 through the expanded access program is very limited, Roche and Trimeris have announced that enrolment in Phase III trials of T-20 is now open to HIV patients who are eligible. More than 20 sites in the US are recruiting for patient participation in the Phase III studies.

Comment

Assigned Places: USA 147, Canada 15, Brazil 65, Mexico 30, Australia 15, France 22, Belgium 15, Germany 15, Italy 18, Sweden 15, Netherlands 15, Switzerland 15, Spain 24, UK 15.

There will be a separate EAP for paediatric patients – 50 patients worldwide.

For reasons unknown Roche first excluded many European countries most notably Portugal from this program. When questioned they say that the figures were allocated “following UNAIDS epidemiology data per country”. UNAIDS data, however, do provide figures for Portugal (36,000 with HIV/AIDS).

Following meetings with European activists at the European Community Advisory Board (ECAB) Roche has found an additional 15 places to allocate to Portugal.

References:

Eron J and others. A 14-day Assessment of the Safety, Pharmacokinetics, and Antiviral Activity of T-1249, a Peptide Inhibitor of Membrane Fusion. Abstract 14. Programs and Abstracts of the 8th Conference on Retroviruses and Opportunistic Infections. Feb 4 – 8, 2001, Chicago, IL.

Lalezari J and others. A Controlled Phase II Trial Assessing Three Doses of T-20 in Combination with Abacavir, Amprenavir, Low Dose Ritonavir and Efavirenz in Non-Nucleoside Naive Protease Inhibitor-Experienced HIV-1 Infected Adults. Abstract LB5. Programs and Abstracts of the 8th Conference on Retroviruses and Opportunistic Infections. February 4 – 8, 2001, Chicago, IL.

Reyes G. Development of CCR5 Antagonists as a New Class of Anti-HIV therapeutic. Session 58. Programs and Abstracts of the 8th Conference on Retroviruses and Opportunistic Infections. February 4 – 8, 2001, Chicago, IL.